82 Chapter 4 the future, there is the potential for different models highlighted in this perspective to be combined to create an optimal in vitro model that can utilize the advantages of different models in concert. For example, by combining LOC technology with porcine lung ECM hydrogels, a physiomimetic acute respiratory distress syndrome model incorporating primary rat mesenchymal stromal cells and AECII has recently been developed [62]. Furthermore, these in vitro models can be improved using techniques such as 3D bioprinting that is rapidly offering several new opportunities such as bioinks with bioactive components and tuneable mechanical properties [85, 86]. The cellular and ECM diversity in the lungs and an increase in the use of human material in research calls for the use of spatio-specific material for defined research questions. An indispensable feature of animal models that is yet to be recapitulated in in vitro models, is the systemic responses that arise from a functioning immune system. The inclusion of immune cells in in vitro models developed for testing novel cellular and molecular interventions will aid in advancing knowledge about local and systemic immune responses associated with lung diseases [87]. Furthermore, development of advanced in vitro models will reduce the dependency on animal models for scientific research. However, to reach this point, adequate characterisation of in vitro models is necessary, which will be discussed in the next section.
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